Mechanisms controlling cell cycle exit upon terminal differentiation

Buttitta, Laura; Edgar, Bruce A.

doi:10.1016/j.ceb.2007.10.004

Cited by 184 publications

(153 citation statements)

References 74 publications

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“…Arrest of or exit from the cell cycle is a precondition for a cell to pass into postmitotic states, such as quiescence, senescence, or terminal differentiation. 37 Studies of murine trophoblast giant cells have shown that terminal differentiation is marked by endoreduplication. 38 However we did not detect an increase in the number of polyploid SGHPL-5 cells after treatment with either CCN.…”

Section: Discussionmentioning

confidence: 99%

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

Kipkeew

Kirsch

Klein

et al. 2016

Cell Adhesion & Migration

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Section: Discussionmentioning

confidence: 99%

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

Kipkeew

Kirsch

Klein

et al. 2016

Cell Adhesion & Migration

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“…This would result in loss of adherence with GBM and with adjacent podocytes, events that are all incompatible with maintaining podocyte function. This is why acquisition of functional specialization in a cell type (or a state of terminal differentiation), such as podocytes, neurons, cardiomyocytes is coupled with the permanent exit from the cell cycle [43] and the arrest in a “postmitotic” state, the molecular bases of which are not completely clarified. Forced re-entry of terminally differentiated cells into the cell cycle is however possible, as demonstrated by a number of experimental manipulations, such as viral infections [44, 45] , overexpression of cyclin D1 and cyclin dependent kinase (CDK)4/6 [46], ectopic expression of the Notch intracellular domain [47], or of elongation factor 2 (E2F) [48], but the consequences are often dramatic.…”

Section: The Podocyte’s Catastrophe: Lost Cell Cycle Controlmentioning

confidence: 99%

Podocyte Mitosis – A Catastrophe

Lasagni

Lazzeri²,

Shankland

et al. 2012

CMM

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Podocyte loss plays a key role in the progression of glomerular disorders towards glomerulosclerosis and chronic kidney disease. Podocytes form unique cytoplasmic extensions, foot processes, which attach to the outer surface of the glomerular basement membrane and interdigitate with neighboring podocytes to form the slit diaphragm. Maintaining these sophisticated structural elements requires an intricate actin cytoskeleton. Genetic, mechanic, and immunologic or toxic forms of podocyte injury can cause podocyte loss, which causes glomerular filtration barrier dysfunction, leading to proteinuria. Cell migration and cell division are two processes that require a rearrangement of the actin cytoskeleton; this rearrangement would disrupt the podocyte foot processes, therefore, podocytes have a limited capacity to divide or migrate. Indeed, all cells need to rearrange their actin cytoskeleton to assemble a correct mitotic spindle and to complete mitosis. Podocytes, even when being forced to bypass cell cycle checkpoints to initiate DNA synthesis and chromosome segregation, cannot complete cytokinesis efficiently and thus usually generate aneuploid podocytes. Such aneuploid podocytes rapidly detach and die, a process referred to as mitotic catastrophe. Thus, detached or dead podocytes cannot be adequately replaced by the proliferation of adjacent podocytes. However, even glomerular disorders with severe podocyte injury can undergo regression and remission, suggesting alternative mechanisms to compensate for podocyte loss, such as podocyte hypertrophy or podocyte regeneration from resident renal progenitor cells. Together, mitosis of the terminally differentiated podocyte rather accelerates podocyte loss and therefore glomerulosclerosis. Finding ways to enhance podocyte regeneration from other sources remains a challenge goal to improve the treatment of chronic kidney disease in the future.

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“…Arabidopsis E2F target genes have been identified by the presence of a conserved E2F DNA sequence binding motif (Vandepoele et al, 2005;Naouar et al, 2009). In addition, pRB proteins are associated with several chromatin modifying complexes whose targets are less well defined (Buttitta and Edgar, 2007;van den Heuvel and Dyson, 2008) but include genes involved in developmental regulation (Korenjak and Brehm, 2005). The immediate consequences of acute downregulation of RBR at the transcriptional level, however, are not well understood.…”

Section: Gene Expression Regulation By Rbrmentioning

confidence: 99%

“…Retinoblastoma(-like) proteins have been implicated in regulatory decisions, most prominently in the regulation of the G1/S transition via E2F/DP transcription factors, which regulate the expression of cell cycle genes Gruissem, 2007;van den Heuvel and Dyson, 2008), and in loading of DNA replication complexes (Bosco et al, 2001;Mukherjee et al, 2009). RB/E2F complexes have also been found to be associated with developmentally regulated promoters in Drosophila melanogaster, mouse, and Caenorhabditis elegans, often in combination with other transcription factors and chromatin modifiers (Korenjak and Brehm, 2005;Buttitta and Edgar, 2007;van den Heuvel and Dyson, 2008). In addition, RB has been implicated in E2F-independent regulatory mechanisms, including direct interaction with subunits of the anaphasepromoting complex during cell cycle exit (Binne et al, 2007).…”

Section: Rbr Homeostasis Is Critical For Meristem Integrity and Functionmentioning

confidence: 99%

ArabidopsisRETINOBLASTOMA-RELATED Is Required for Stem Cell Maintenance, Cell Differentiation, and Lateral Organ Production

et al. 2010

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Several genes involved in the regulation of postembryonic organ initiation and growth have been identified. However, it remains largely unclear how developmental cues connect to the cell cycle. RETINOBLASTOMA RELATED (RBR) is a plant homolog of the tumor suppressor Retinoblastoma (pRb), which is a key regulator of the cell cycle. Using inducible RNA interference (RNAi) against Arabidopsis thaliana RBR (RBRi), we reduced RBR expression levels at different stages of plant development. Conditional reduction or loss of RBR function disrupted cell division patterns, promoted context-dependent cell proliferation, and negatively influenced establishment of cell differentiation. Several lineages of toti-and pluripotent cells, including shoot apical meristem stem cells, meristemoid mother cells, and procambial cells, failed to produce appropriately differentiated cells. Meristem activity was altered, leading to a disruption of the CLAVATA-WUSCHEL feedback loop and inhibition of lateral organ formation. Release of RBR from RNAi downregulation restored meristem activity. Gene profiling analyses soon after RBRi induction revealed that a change in RBR homeostasis is perceived as a stress, even before genes regulated by RBR-E2F become deregulated. The results establish RBR as a key cell cycle regulator required for coordination of cell division, differentiation, and cell homeostasis. INTRODUCTIONRetinoblastoma (RB) was the first tumor suppressor gene identified in animals (Friend et al., 1986) and later was associated with cell cycle regulation, thus establishing pRb as a key regulator of cell proliferation. In animals, three members of the RB family of proteins (pRb, p107, and p130), also referred to as pocket proteins (Mulligan and Jacks, 1998), negatively regulate the G1-to-S phase transition during the cell cycle. It is now widely accepted that mitogenic signals activate several cyclin-dependent kinase (CDK)-cyclin complexes during progression through G1 to phosphorylate pRb, thereby releasing it from interactions with E2F/DP transcription factor complexes to facilitate S-phase entry (Weinberg, 1995). Subsequently, pRb was also found to regulate tissue-specific transcription factors that regulate cell differentiation, such as MyoD, which activates muscle-specific genes (De Falco et al., 2006). pRb also regulates germ cell proliferation, differentiation, and survival (Toppari et al., 2003) and is required for osteoblast, keratinocyte, and macrophage differentiation (Nead et al., 1998;Liu et al., 1999;Thomas et al., 2003). Together with the tumor suppressor p53, pRb regulates adipocyte differentiation and function (Hallenborg et al., 2009). The requirement for RB in cell differentiation therefore extends beyond regulation of cell cycle entry. For example, the loss of RB function in cardioblasts affects cell differentiation by modulating the activity of cardiogenic factors (Papadimou et al., 2005).RB-related genes, termed RETINOBLASTOMA-RELATED (RBR; Ach et al., 1997), are also found in monocots (Grafi et al., 1996;Xie et al...

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Mechanisms controlling cell cycle exit upon terminal differentiation

Cited by 184 publications

References 74 publications

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

Podocyte Mitosis – A Catastrophe

ArabidopsisRETINOBLASTOMA-RELATED Is Required for Stem Cell Maintenance, Cell Differentiation, and Lateral Organ Production

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